Adipose-derived protein Acrp30 is a recently identified hormone released from fat tissue that has a role in glucose metabolism, but its molecular effects remain elusive. In December 15 Journal of Clinical Investigation, Terry Combs and colleagues from Albert Einstein College of Medicine, Bronx, New York, show that a moderate rise in circulating levels of Acrp30 inhibits both the expression of hepatic gluconeogenic enzymes and the rate of endogenous glucose production.

Combs et al. studied the effects of purified recombinant Acrp30 on mice during a pancreatic euglycemic clamp. They found that glucose flux through glucose-6-phosphatase (G6Pase) decreased with Acrp30, whereas the activity of the direct pathway of glucose-6-phosphate biosynthesis, an index of hepatic glucose phosphorylation, increased significantly. In addition Northern blot analyses pointed to the gluconeogenic enzymes PEPCK and G6Pase as potential molecular targets of Acrp30 in the liver (J Clin Invest 2001, 108:1875-1881).

The authors...